Analysis of a large single institution cohort of related donors fails to detect a relation between SDF1/CXCR4 or VCAM/VLA4 genetic polymorphisms and the level of hematopoietic progenitor cell mobilization in response to G-CSF.
Adult
Aged
Chemokine CXCL12
/ genetics
Female
Granulocyte Colony-Stimulating Factor
/ administration & dosage
Hematopoietic Stem Cell Mobilization
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
/ drug effects
Humans
Integrin alpha4beta1
/ genetics
Living Donors
Male
Middle Aged
Polymorphism, Single Nucleotide
Receptors, CXCR4
/ genetics
Transplantation, Homologous
Vascular Cell Adhesion Molecule-1
/ genetics
Young Adult
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
09
07
2019
accepted:
24
01
2020
entrez:
6
3
2020
pubmed:
7
3
2020
medline:
13
6
2020
Statut:
epublish
Résumé
We studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. All donors were homogeneously cared for at a single institution, and received rhG-CSF as a mobilization treatment prior to undergoing apheresis. Peripheral blood CD34+ cell counts were used as the main surrogate marker for rhG-CSF induced mobilization. We searched whether inter-individual variations in known genetic polymorphisms located in genes whose products are functionally important for mobilization, could affect the extent of CD34+ mobilization, either individually or in combination. We found little or no influence of individual SNPs or haplotypes for the SDF1, CXCR4, VCAM and VLA4 genes, whether using CD34+ cell counts as a continuous or a categorical variable. Simple clinical characteristics describing donors such as body mass index, age and possibly sex are more potent predictors of stem cell mobilization. The size of our cohort remains relatively small for genetic analyses, however compares favorably with cohorts analyzed in previously published reports suggesting associations of genetic traits to response to rhG-CSF; notwithstanding this limitation, our data do not support the use of genetic analyses when the choice exists of several potential donors for a given patient.
Identifiants
pubmed: 32134938
doi: 10.1371/journal.pone.0228878
pii: PONE-D-19-19237
pmc: PMC7058310
doi:
Substances chimiques
CXCL12 protein, human
0
CXCR4 protein, human
0
Chemokine CXCL12
0
Integrin alpha4beta1
0
Receptors, CXCR4
0
Vascular Cell Adhesion Molecule-1
0
Granulocyte Colony-Stimulating Factor
143011-72-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0228878Déclaration de conflit d'intérêts
Both Dr Sylvain Garciaz and myself Christian Chabannon received funding from SANOFI S.A. as speakers during industry-sponsored symposium. I also benefited of an invitation – including financial support for traveling – to a scientific meeting as a delegate. In addition, SANOFI S.A. funded another and different clinical project on autologous stem cell mobilization and collection that was conducted at Institut Paoli-Calmettes, the Comprehensive Cancer Center in Marseille, France. This does not alter our adherence to PLOS ONE policies on sharing data and materials (as detailed online in the journal guide for authors http://journals.plos.org/plosone/s/competinginterests).
Références
Transfus Apher Sci. 2017 Apr;56(2):154-159
pubmed: 27839966
Biol Blood Marrow Transplant. 2014 Sep;20(9):1418-25
pubmed: 24892261
PLoS One. 2015 Mar 24;10(3):e0121859
pubmed: 25803672
J Clin Invest. 2000 Dec;106(11):1331-9
pubmed: 11104786
Haematologica. 2016 Feb;101(2):256-62
pubmed: 26565001
Tissue Antigens. 2011 Mar;77(3):193-200
pubmed: 21299523
Drug Metab Rev. 2015 Aug;47(3):281-90
pubmed: 25996670
Stem Cells. 2009 Apr;27(4):836-7
pubmed: 19350684
Biol Blood Marrow Transplant. 2013 Oct;19(10):1517-21
pubmed: 23891749
J Clin Invest. 2000 Jan;105(1):101-11
pubmed: 10619866
Blood. 1997 Dec 15;90(12):4779-88
pubmed: 9389694
Haematologica. 2011 Jan;96(1):102-9
pubmed: 20851866
Tissue Antigens. 2010 Jul;76(1):18-30
pubmed: 20331842
Am J Hematol. 2017 Apr;92(4):E57-E59
pubmed: 28133837
Curr Drug Metab. 2012 Sep 1;13(7):991-9
pubmed: 22591347
PLoS One. 2016 Oct 4;11(10):e0163570
pubmed: 27701438
Vox Sang. 2005 Nov;89(4):229-35
pubmed: 16262756
Evol Bioinform Online. 2016 Feb 21;11(Suppl 2):19-26
pubmed: 26917942
Exp Hematol. 2016 Jul;44(7):567-73
pubmed: 27106798
J Clin Apher. 2008;23(6):171-7
pubmed: 18988229